Assessment of Eptifibatide Dosing in Renal Impairment Before and After In-Service Education Provided by Pharmacists

BACKGROUND: Anticoagulant and antithrombotic agents are frequently cited as sources of medication errors. Several factors increase the risk of receiving excess dosing of glycoprotein IIb/IIIa inhibitors in the management of acute coronary syndrome (ACS), including older age, female gender, elevated serum creatinine, a history of diabetes mellitus, and a history of heart failure. In June 2003, the manufacturer of eptifibatide released a recommendation adjusting infusion rate downward to 1 mcg per kg per minute for eptifibatide in patients with renal impairment, defined as an estimated creatinine clearance (CrCl) less than 50 ml per minute. Eptifibatide is known to accumulate in patients with renal impairment, thereby increasing hemorrhagic risk. OBJECTIVES: To assess the impact of education on physician adherence to the renal dosing recommendation for eptifibatide at 2 academic medical centers. The primary outcome measure was the proportion of patients with renal impairment dosed appropriately with eptifibatide before and after in-service education provided by a clinical pharmacist. Secondary outcome measures included the difference in the improvement in dosing adherence between the 2 sites and the influence of patient variables on the incidence of bleeding events. METHODS: This prospective study was conducted in patients with renal impairment who received eptifibatide for the medical management of unstable angina (UA) or non ST-elevation myocardial infarction (NSTEMI) or for the interventional management of chronic stable angina, UA, NSTEMI, or ST-elevation myocardial infarction (STEMI, not a Food and Drug Administration-approved use). Patient data were assessed at 2 tertiary care teaching institutions between June 2003 and December 2005. The preeducation phase for the sites ran from June 2003 through April 2005 for Site A and from June 2003 through May 2005 for Site B. The posteducation phase ran from May 2005 through December 2005 for Site A and from June 2005 through December 2005 for Site B. At site A, a 1-hour educational seminar on ACS management strategies was employed, in which 5 minutes focused on adherence of prescribers to the guideline for renal dosing recommendations for eptifibatide. This tutorial was accomplished through (1) an in-service provided by 1 clinical pharmacist to the cardiology department, and (2) handouts containing the renal dosing recommendations for eptifibatide along with dosing for other medications used to manage ACS. The intervention at Site B involved an eptifibatide-focused seminar presented to cardiologists by a clinical pharmacist, 10 minutes of which was devoted to renal dosing recommendations that included (1) a summary of literature supporting the infusion rate reduction in patients with renal impairment and (2) the specific updated dosing recommendation for eptifibatide. The data collected in retrospective chart review included patient demographics, baseline laboratory values, and risk factors for bleeding. An appropriate eptifibatide dose was defined as a physician order for a continuous infusion of 1 mcg per kg per minute in patients with an estimated CrCl less than 50 ml per minute. RESULTS: A total of 148 patients with renal impairment who received eptifibatide were evaluated (106 in the preeducation phase and 42 in the posteducation phase). A significant increase in the adherence rate for eptifibatide dosing in patients with renal impairment was observed from 36.8% in the preeducation phase to 69.0% in the posteducation phase (P less than 0.001) for the 2 sites combined. The incidence of major and minor bleeding was 16.7% in the preeducation phase and 14.3% in the posteducation phase (P=0.742). When bleeding incidence was stratified by the appropriateness of infusion, the incidence of major and minor bleeding was also similar for appropriate dosing (1 mcg per kg per minute, 16.4%) versus inappropriate dosing (2 mcg per kg per minute, 15.7%.

OBJECTIVE: To assessthe impact of education on physicianadherence to therenal dosing recommendation foreptifibatide at 2academic medical centers.The primary outcomemeasurewas theproportionofpatients with renalimpairmentdosed appropriately with eptifibatide beforeand after in-service education providedbyaclinicalpharmacist. Secondary outcome measures included thedifference in theimprovement in dosing adherence between the2sitesand theinfluence of patientvariables on theincidence of bleedingevents. At site A, a1-hour educational seminaronACS management strategies wasemployed, in which5minutesfocused on adherence of prescribers to theguideline forrenal dosing recommendationsfor eptifibatide.This tutorialwas accomplished through(1) an in-service providedby1clinical pharmacisttothe cardiology department, and(2) handouts containingthe renaldosingrecommendationsfor eptifibatide alongwithdosingfor other medicationsusedtomanageACS.
CONCLUSION:Thiseducational intervention providedbyaclinicalpharmacist wasassociated with improved prescriberadherence to dosing recommendations foreptifibatide in patients with renalimpairment. Improved adherence to the dosing guideline andadministration of an appropriateinfusionrate were not associated with reductionineitherminor or majorbleedingevents.

What is alreadyknown aboutthissubject
What this studyadds •U se of platelet glycoproteinIIb/IIIainhibitorsinpatientswith non-ST-segment-elevation ACSr educes ischemic complicationsbeforeand after percutaneous coronary intervention but is associated with an increased risk of bleeding, ande ven greaterh emorrhagic risk has been reported in patients with renal impairment.
•T he acutenature in whicheptifibatideispreparedand administeredinthe cardiaccatheterization laboratory or emergency department does notpermitp harmaciste valuationo rthe use of acomputerized dosing system.
•T herea re 2c ommont ypes of interventionsi ntendedt o improve adherence to medication dosing guidelines:education programsand computerized dosing aids.
•T hisi nterventioni nvolving pharmacist-directed educationo f prescriberst or educet he dose of eptifibatide to 1m cg perk g perm inutef or patients with renal impairment wasa ssociated with improveda dherence to thed osingr ecommendation( the intermediate,process outcome)but no change in theproportion of patients whoexperienced major or minor bleeding episodes (end point, clinicaloutcome). These resultscannotbeattributed to theintervention, sincethisstudy lacked acontrol group.
Review of therenal dosing of eptifibatide occurred over 5minutes during thep resentationa nd covered thei nfusionr atea djustment andthe useo fC rClini dentifying an appropriate infusionrate. A pocketreference card thatincludedrenal dosing recommendations foreptifibatidewas distributed.The in-service presentation at Site A wasattendedbyapproximately 80%ofthe cardiology department andincludedcardiologists, nurses,and houseofficers.

Bleeding
Afterr emovingd ataf or patients whow ento nt oC ABG, we included 131p atientsi nt he initialb leedinga nalysis. Data for patients whor eceivedCABGw erer emoved in accordance with theT IMI bleeding criteria,a st he transfusion requirements for this population skew bleeding results. At otal of 11 minor and 10 majorbleedingeventsoccurred.

Limitations
Firsta nd foremost amongt he limitations of this studyw as the absenceofacontrol group. Therefore, we cannotbecertain that oure ducationali ntervention was ther easonf or thei mproved adherencetothe dosing guidelineinpatientswithrenal impairment.Second,wechose to define theprimary outcome measure as an intermediate measure (infusiona ppropriateness)a nd the proportion of patients whoexperienced either amajor or minor bleeding episode as thes econdary outcome.O ur assumption wast hata dherence to renal dosing recommendations would result in adecreaseinhemorrhagic complications. Third, thes mall andu nequal samples izes in thep reeducation andp osteducationp hases contributed to thea bsence of as ignificant differencei nt he i ncidence of minor andm ajor hemorrhagice ventsi nt hisa nalysis. Logistic regression demonstrated an increasedl ikelihood of bleeding in patients >80 years. We anticipated an increasedr isko fb leedingi np atients in whom eptifibatides erum concentration should be elevated (history of chronicrenal failure,CrCl<30 ml perminute, inappropriatei nfusionr ate, prolongedi nfusion).H owever,n oneo f thesef actors wasa ssociated with increasing patients'b leeding risk,mostlikelydue to thesmall sample size in ourstudy.